BSP :: Recent Patents on Inflammation & Allergy Drug Discovery Home Page

Contents

VEGF, Angiopoietin-1 and -2 in Bronchial Asthma: New Molecular Targets in Airway Angiogenesis and Microvascular Remodeling Pp. 1-8
Hiroshi Kanazawa
[Abstract] [Full Text Article]

CD48 as a Novel Target in Asthma Therapy Pp. 9-12
Ariel Munitz, Ido Bachelet and Francesca Levi-Schaffer
[Abstract] [Full Text Article]

Novel Strategies for the Treatment of Asthma Pp. 13-19
Hajime Takizawa
[Abstract] [Full Text Article]

Anti-Tumor Necrosis Factor-Alpha (TNF-α) Treatment Strategies in Crohn’s Disease Pp. 21-34
Jean-Marie Reimund, Julia Ratajczyk, Christian D. Muller, Brigitte Sola and Anne-Marie Justum
[Abstract] [Full Text Article]

Allergic Inflammation and the Oral Mucosa Pp. 35-38
Cristoforo Incorvaia, Franco Frati, Laura Sensi, Gian Galeazzo Riario-Sforza and Francesco Marcucci
[Abstract] [Full Text Article]

Infectious Complications with Anti-TNFα Therapy in Rheumatic Diseases: A Review Pp. 39-47
Éric Toussirot, Gérald Streit and Daniel Wendling
[Abstract] [Full Text Article]

A Review of Recent Patents Concerning Therapy of Respiratory Diseases Using Gene Silencing by RNAi (RISC) and EGS (RNAse P) Pp. 49-55
David H. Dreyfus and Lucy Ghoda
[Abstract] [Full Text Article]

Targeting the Toll-System in Cardiovascular Sciences Pp. 57-67
Gábor Földes, Stephan von Haehling, Ewa A. Jankowska and Stefan D. Anker
[Abstract] [Full Text Article]

Febuxostat: A Novel Non-Purine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Gout Pp. 69-75
Kuang-Hui Yu
[Abstract] [Full Text Article]

Recent Patents in Pemphigus Research, Prophylaxis, Diagnosis and Treatment in USA (1988-2006) Pp. 77-81
Daisuke Tsuruta and Hiromi Kobayashi
[Abstract] [Full Text Article]

Incomplete Invention of Drugs Pp. 83-86
Tomoyuki Hisa
[Abstract] [Full Text Article]

Patent Annotations Pp. 87-90

Patent Selections Pp. 91-94

Abstracts

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VEGF, Angiopoietin-1 and -2 in Bronchial Asthma: New Molecular Targets in Airway Angiogenesis and Microvascular Remodeling
Hiroshi Kanazawa

[Full Text Article]

Airway angiogenesis and microvascular remodeling are known features of bronchial asthma, but the mechanisms of these structural alterations are just beginning to be elucidated. Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, stimulates endothelial cell proliferation and induces the angiogenesis. Recently, considerable attentions have been devoted to the physiological roles of angiopoietin (Ang)-1 and -2 as regulatory factors of VEGF. Ang-1 has been shown to induce the migration and sprouting of endothelial cells, and coexpression of Ang-1 and VEGF enhanced angiogenesis. In the presence of high levels of VEGF, Ang-2 also promotes rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulates sprouting of new blood vessels. Thus, VEGF, Ang-1 and -2 may play complementary and coordinated roles in airway angiogenesis and microvascular remodeling, and these structural changes are potentially reversible by therapeutic intervention. The scope of the present review is to discuss from a clinical point of view the potential interactions between VEGF and angiopoietins in the asthmatic airways, and focus on the therapeutic implications targeting for these angiogenic factors. Recently, there is an increasing number of patents which have been focused on the inhibitors of VEGF action. These inhibitors are directed towards the receptors of VEGF or intracellular substrates for the receptors. We will also discuss several patents regarding inhibitors of VEGF action in the present review.

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CD48 as a Novel Target in Asthma Therapy
Ariel Munitz, Ido Bachelet and Francesca Levi-Schaffer

[Full Text Article]

CD48, a CD2-related surface molecule, emerges as a critical effector molecule in immune responses. CD48 has a striking array of biological functions, among them adhesion, pathogen recognition, cellular activation, and cytokine regulation. Still, it is surprising that this mysterious molecule has not yet met its proper use as a therpeutical target in exaggerated immune disorders like hematopoietic tumors, autoimmunity and allergic reactions. Recently, CD48 was investigated in our laboratory as an effector molecule in human eosinophil function and in asthma. In this review, we shall discuss the known aspects of CD48 biology and describe the recent advances regarding the role of CD48 in human disease. Moreover, we shall review inventions making use of CD48, and discuss recent patents and the potential of CD48 as a future target for the therapy of allergic and other diseases.

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Novel Strategies for the Treatment of Asthma
Hajime Takizawa

[Full Text Article]

It is now clear that airway inflammatory processes characterized by eosinophils and Th2 lymphocytes are pivotal as the pathological features of asthma. Standard inhaled corticosteroids markedly suppress such inflammatory changes, resulting in clinical beneficial effects. However, it is also notified that airway wall remodeling including goblet cell hyperplasia, sub-epithelial collagen deposits, increased capillary networks and smooth muscle hypertrophy occur as a chronic consequence of this disorder even by the recommended strategies with steroid treatment. These pathologic changes play an important role in the increased airway obstruction and hyperresponsiveness, and eventually in the development of irreversible respiratory failure. Recent studies have elucidated that myofibroblasts and smooth muscle as well as mucosal epithelial cells play a vital role in these processes. Agents regulating proliferation, differentiation and activity of these cells, especially of low-molecular weight compounds, attract attention. Studies on molecular mechanisms of above processes, have led the development and patents of potential drugs including inhibitors of NF kappaB, statins, macrolides and phosphodiesterase-4 inhibitors.

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Anti-Tumor Necrosis Factor-Alpha (TNF-α) Treatment Strategies in Crohn’s Disease
Jean-Marie Reimund, Julia Ratajczyk, Christian D. Muller, Brigitte Sola and Anne-Marie Justum

[Full Text Article]

Crohn’s disease is a complex multifactorial disorder characterized by the alternation of a cytokine-driven T-lymphocyte-depending inflammation of the intestinal mucosa, and “off” periods, where patients are completely asymptomatic. Although all the causative factors have not been clearly identified, the continuously growing understanding of the major abnormalities of the inflammatory and immune response leading to the often debilitating symptoms reported by Crohn’s disease patients, improves our capacity to characterize new potential therapeutic targets with the subsequent hope to discover new (more efficient and less toxic) drugs. Saying that, in the recent years, tumor necrosis factor-alpha undoubtedly emerges as a key cytokine involved in Crohn’s disease pathogenesis, and constant efforts have been made to control tumor necrosis factor-alpha deleterious effects in Crohn’s disease. This review schematically summarizes the current understanding of tumor necrosis factor-alpha’s role in Crohn’s disease pathogenesis as well as the present and the future treatment strategies which may be helpful in patients by inhibiting tumor necrosis factor-alpha production and effects. Beside drugs under investigation, several original approaches are described or mentioned, most of them leading to recent patents such as polyclonal anti-TNF-α antibodies from avian origin, allowing potentially oral administration, or combination strategies such as vitamin D and anti-TNF-α antibodies or methotrexate and anti-TNF-α antibodies, or decoy oligodeoxynucleotides interfering with the binding of nuclear factor-κB to its target genes promoters.

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Allergic Inflammation and the Oral Mucosa
Cristoforo Incorvaia, Franco Frati, Laura Sensi, Gian Galeazzo Riario-Sforza and Francesco Marcucci

[Full Text Article]

Allergic inflammation is initiated by the contact between allergen(s) and specific IgE antibodies, driven by regulatory cells such as antigen presenting cells and T lymphocytes, which orientate and orchestrate the response, and sustained by effector cells such as mast cells, basophils, and eosinophils. Among tissues and organs targeted by allergy, the nose, the lungs and the skin have the property to spread in distant sites the initially local reaction, thus resulting in systemic disease. By contrast, the oral mucosa seems to be a tolerogenic site regarding the immunologic response to allergens. This mucosa is characterized by abundance of dendritic cells, which are antigen presenting cells specialized in uptaking, processing and presenting the antigens to T cells, and particularly to T regulatory cells which in turn can downregulate Th1 and Th2 immune responses by direct cell contact or by production of immunosuppressive cytokines.

The other important aspect of the oral mucosa is the negligible presence of effector inflammatory cells, namely mast cells and eosinophils, which accounts for the reportedly good safety of sublingual administration of allergen immunotherapy. These peculiar aspects and patents have important implications in treatment and prevention of allergic diseases.

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Infectious Complications with Anti-TNFα Therapy in Rheumatic Diseases: A Review
Éric Toussirot, Gérald Streit and Daniel Wendling

[Full Text Article]

TNFα plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFα antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFα therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFα inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFα inhibitors related infections were described in the randomized clinical trials, and were then declared to post-marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFα antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFα inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

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A Review of Recent Patents Concerning Therapy of Respiratory Diseases Using Gene Silencing by RNAi (RISC) and EGS (RNAse P)
David H. Dreyfus and Lucy Ghoda

[Full Text Article]

This article will review recent developments in the field of gene silencing as a therapy for respiratory and related inflammatory and immunologic diseases. The respiratory epithelium offers an attractive target for therapies derived from nucleic acids since the respiratory epithelium contains endogenous lipids that can facilitate uptake of polar nucleic acids and related compounds. Both RNAi (RNA Interference) in which a messenger RNA (mRNA) is targeted by an endogenous enzyme complex termed RISC (RNA Interference Silencing Complex, also previously termed RNA Induced Silencing Complex in earlier references) and also gene silencing using EGS (External Guide Sequences) in which a messenger RNA (mRNA) is targeted by an endogenous RNA enzyme termed RNase P are summarized including selected patents. The strengths and limitations of these technologies such as problems of delivery to specific tissues and potential for non-specific inflammatory response and off-targeting are compared. The possibility of therapy designed exploit synergies between both RISC and RNAse P and therapeutic benefits of inhibiting either or both pathways are also considered.

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Targeting the Toll-System in Cardiovascular Sciences
Gábor Földes, Stephan von Haehling, Ewa A. Jankowska and Stefan D. Anker

[Full Text Article]

Toll-like receptors (TLRs) are a family of pattern recognition receptors that serve as a key part of the innate immune system. TLRs play a role in coordinating the organism's first line of defence against invading microbes or tissue injury. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical disorders. Among these processes are cardiovascular disorders such as atherosclerosis, heart failure, viral myocarditis or diabetic angiopathies. In the new area of TLRs, this has generated a lot of interest from pharmaceutical companies as well as the investment communities. The improved understanding of TLRs, their key ligands and signaling cascades brought a number of diagnostic methods and compounds into clinical development. The first potential applications for TLR compounds include therapies for cardiovascular disease. The idea of this article is to describe the molecular basis of TLR signaling and review corresponding new inventions relating to TLR system and drug targets in cardiovascular disease.

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Febuxostat: A Novel Non-Purine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Gout
Kuang-Hui Yu

[Full Text Article]

Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. To critically review the clinical trial data, safety profile, pharmacology, and role of febuxostat for the treatment of hyperuricemia and gout.

A review of the literatures on febuxostat was performed. All available human studies describing the pharmacology of febuxostat were included; including pharmacodynamics, efficacy, and safety of febuxostat. Available studies, patents and abstracts were identified through PubMed (1990-December 2006), Delphion, Cochrane Databases, and the American College of Rheumatology and European League Against Rheumatism Web sites. Key search terms were febuxostat, TMX-67, and TEI-6720. Febuxostat has been used at a dose of 80 to 120 mg for the management of hyperuricemia in gout. The drug is mainly metabolized by the liver and therefore mild-moderate renal impairment does not appear to impede its effect. However, given the limited long-term liver function safety data, failure of a large percentage of patients taking febuxostat to achieve the primary end point of serum urate levels less than 6.0 mg/dL, and higher drop out rate in the Febuxostat group in the clinical trials, the exact role of febuxostat as a urate-lowering therapy remains uncertain. Febuxostat is a promising alternative to allopurinol for the treatment of gout and hyperuricemia. The optimal length of colchicines prophylactic therapy for chronic gout, clinical significance of abnormal liver function tests results during therapy, and safety in patients with moderate or severe hepatic and renal insufficiency warrant further investigation. A post-market surveillance is also needed to address the safety issue of long-term febuxostat treatment.

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Recent Patents in Pemphigus Research, Prophylaxis, Diagnosis and Treatment in USA (1988-2006)
Daisuke Tsuruta and Hiromi Kobayashi

[Full Text Article]

Pemphigus is an autoimmune blistering disease which is characterized histologically by intraepidermal blisters due to separation of epidermal cell-cell contacts, and immunopathologically by circulating IgG type autoantibodies directed against the desmosomes, which is the cell-cell attachment device in the epidermis. This review briefly summarizes current concepts of conventional diagnosis and treatment of pemphigus, and then focuses on recent US patents related to Pemphigus research, prophylaxis, and diagnosis and treatment from 1988 to 2006. As a result, possible new therapeutic approaches, prophylaxis, diagnostic procedures, or experimental models for the Pemphigus have been disclosed.

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Incomplete Invention of Drugs
Tomoyuki Hisa

[Full Text Article]

Scientists seldom know the differences between “rejected invention”, “non-invention”, “incomplete invention”, “invention yet to be completed” and “defective invention”. The Japanese Supreme Court appointed me as a specialist member (Article 92-2, Code of Civil Procedure) of intellectual property division for medical and biological patents. Herein, I present scientists to the differences and which of them are patentable. In order to prevent oneself from being taken for granted for the scientists’ noblesse oblige by clever business administrations, the scientists must know the borderline between patentable or non-patentable.